determination-procoagulant-activity-extracellular-vesicle-ev-using-ev

Determination of the Procoagulant Activity of Extracellular Vesicle (EV) Using EV-Activated Clotting Time (EV-ACT)

The role of extracellular vesicles (EV) in various diseases is gaining increased attention, particularly due to their potent procoagulant activity. ...

Tianjin Medical University General Hospital

Recent studies have reported increased mortality for right-sided colon cancers; however, the results are conflicting for different stage tumors. We examined the differences in clinicopathology between right- and left-sided colon cancers and the relationships between colon cancer location (right- and left-side) and 5-year disease-free survival (DFS) and overall survival (OS).

Comparison of 627 patients with right- and left-sided colon cancer in China: Differences in clinicopathology, recurrence, and survival.

A retrospective study was conducted to assess the efficacy and toxicity of lobaplatin-etoposide (EL) chemotherapy for small cell lung cancer (SCLC).

Retrospective study of the efficacy and toxicity of lobaplatin-etoposide chemotherapy in small cell lung cancer.

Lung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) accounts for 80%-85% of lung cancer. Malignant tumors can proliferate indefinitely, and cell cycle regulation is abnormal which is one of the characteristics of malignant tumor. Cyclin D-dependent kinase (CDK) 4/6 inhibitor can prevent tumor cells from entering S phase through G₁ phase and inhibit tumor proliferation. The CDK4/6 inhibitor has achieved good effect in hormone receptor positive breast cancer, and CDK4/6 inhibitor combined with endocrine therapy has become a standard treatment for this kind of patients. Cell cycle regulation is usually abnormal in NSCLC, which incidence is about 22%-45%. CDK4/6 inhibitors have also carried out a series of research and achieved some results, which may become a new treatment in the future. This review focuses on the research progress of CDK4/6 inhibitors in NSCLC, including the mechanism and the approved drugs, clinical research progress in NSCLC, biomarkers for efficacy prediction and current limitations.

[Research Progress of CDK4/6 Inhibitors in Non-small Cell Lung Cancer].

The third-generation EGFR-TKI, represented by osimertinib, has been widely used in clinical practice; however, resistance eventually emerges. At present, it remains unclear whether an abnormal cell cycle is involved in acquired resistance, and whether the combination of palbociclib (CDK4/6 inhibitor) and osimertinib can overcome the third-generation TKI resistance.

CDK4/6 inhibitor palbociclib overcomes acquired resistance to third-generation EGFR inhibitor osimertinib in non-small cell lung cancer (NSCLC).

The third-generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), represented by osimertinib, has achieved remarkable clinical outcomes in the treatment of non-small-cell lung cancer (NSCLC) with EGFR mutation. However, resistance eventually emerges in most patients and the underlying molecular mechanisms remain to be fully understood. In this study, we generated an osimertinib-acquired resistant lung cancer model from a NSCLC cell line H1975 harboring EGFR L858R and T790M mutations. We found that the capacity of DNA damage repair was compromised in the osimertinib resistant cells, evidenced by increased levels of γH2AX and higher intensity of the comet tail after withdrawal from cisplatin. Pharmacological inhibiting the activity or genetic knockdown the expression of DNA-PK, a key kinase in DNA damage response (DDR), sensitized the resistant cells to osimertinib. Combination of osimertinib with the DNA-PK inhibitor, PI-103, or NU7441, synergistically suppressed the proliferation of the resistant cells. Mechanistically, we revealed that DNA-PK inhibitor in combination with osimertinib resulted in prolonged DNA damage and cell cycle arrest. These findings shed new light on the mechanisms of osimertinib resistance in the aspect of DNA repair, and provide a rationale for targeting DNA-PK as a therapeutic strategy to overcome osimertinib-acquired resistance in NSCLC.

Targeting DNA-PK overcomes acquired resistance to third-generation EGFR-TKI osimertinib in non-small-cell lung cancer.

The resistance mechanism of the third generation of epidermal growth factor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is complex. Epithelial mesenchymal transition (EMT) is a common mechanism of EGFR-TKI acquired resistance. Snail is an important transcription factor related to EMT. Whether targeting Snail can reverse the resistance of osimertinib by downregulating Snail is unknown.

Targeting the EMT transcription factor Snail overcomes resistance to osimertinib in EGFR-mutant non-small cell lung cancer.

Brain metastasis is common in patients with lung cancer and has a negative impact on overall survival (OS). The aim of this study was to investigate therapeutic effects and prognosis-related factors for survival of patients with pulmonary adenocarcinoma and brain metastasis.

Article	Year
Comparison of 627 patients with right- and left-sided colon cancer in China: Differences in clinicopathology, recurrence, and survival. Chronic diseases and translational medicine\| PubMed ID: 29063056	2017
Retrospective study of the efficacy and toxicity of lobaplatin-etoposide chemotherapy in small cell lung cancer. Thoracic cancer\| PubMed ID: 30600898	2019
[Research Progress of CDK4/6 Inhibitors in Non-small Cell Lung Cancer]. Zhongguo fei ai za zhi = Chinese journal of lung cancer\| PubMed ID: 32102134	2020
CDK4/6 inhibitor palbociclib overcomes acquired resistance to third-generation EGFR inhibitor osimertinib in non-small cell lung cancer (NSCLC). Thoracic cancer\| PubMed ID: 32677256	2020
Targeting DNA-PK overcomes acquired resistance to third-generation EGFR-TKI osimertinib in non-small-cell lung cancer. Acta pharmacologica Sinica\| PubMed ID: 33414509	2021
Targeting the EMT transcription factor Snail overcomes resistance to osimertinib in EGFR-mutant non-small cell lung cancer. Thoracic cancer\| PubMed ID: 33943009	2021
The role of brain metastases in patients with pulmonary adenocarcinoma: a retrospective study. Annals of palliative medicine\| PubMed ID: 35016418	2021

Qiong Qin

Biography

JoVE Journal Publications

Other Publications